Pneumococcal Nasopharyngeal Carriage Research Articles

Nasopharyngeal carriage of Streptococcus pneumoniae in Latin America and the Caribbean: A systematic review and meta-analysis.

Streptococcus pneumoniae is a leading cause of morbidity and mortality globally, causing bacteremic pneumonia, meningitis, sepsis, and other invasive pneumococcal diseases. Evidence supports nasopharyngeal pneumococcal carriage as a reservoir for transmission and precursor of pneumococcal disease. To estimate the pneumococcal nasopharyngeal burden in all age groups in Latin America and the Caribbean (LAC) before, during, and after the introduction of pneumococcal vaccine conjugate (PVC). Systematic literature review of international, regional, and country-published and unpublished data, together with reports including data from serotype distribution in nasopharyngeal carriage in children and adults from LAC countries following Cochrane methods. The protocol was registered in PROSPERO database (ID: CRD42023392097). We included 54 studies with data on nasopharyngeal pneumococcal carriage and serotypes from 31,803 patients. In children under five years old, carriage was found in 41% and in adults over 65, it was 26%. During the study period, children under five showed a colonization proportion of 34% with PCV10 serotypes and 45% with PCV13 serotypes. When we analyze the carriage prevalence of PCV serotypes in all age groups between 1995 and 2019, serotypes included in PCV10 and those included in PCV13, both showed a decreasing trend along analysis by lustrum. The data presented in this study highlights the need to establish national surveillance programs to monitor pneumococcal nasopharyngeal carriage to monitor serotype prevalence and replacement before and after including new pneumococcal vaccines in the region. In addition, to analyze differences in the prevalence of serotypes between countries, emphasize the importance of approaches to local realities to reduce IPD effectively.

Nasopharyngeal Carriage of Streptococcus pneumoniae in Tunisian Healthy under-Five Children during a Three-Year Survey Period (2020 to 2022).

We aimed to assess the prevalence of nasopharyngeal pneumococcal carriage and to determine serotype distribution, antibiotic susceptibility patterns, and evolutionary dynamics of Streptococcus pneumoniae isolates in healthy under-five children. Nasopharyngeal swabs were collected from healthy children over three survey periods between 2020 and 2022. All pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. A total of 309 S. pneumoniae isolates were collected, with an overall prevalence of nasopharyngeal pneumococcal carriage of 24.4% (CI95%: [22-26.8%]). These isolates were classified into 25 different serotypes. The most common serotypes were 14 (14.9%), 19F (12%), 6B (10.4%), and 23F (7.4%), which are covered by the PCV10 vaccine, as well as 19A (8.4%) and 6A (7.8%), which are covered by the PCV13 vaccine. A significant decrease in the proportion of serotype 19F (p = 0.001) and an increase in serotypes 19A (p = 0.034) and 6A (p = 0.029) were observed between the three survey periods. Multidrug resistance (MDR) was noted for 56.6% of the isolates. A significant association with antimicrobial resistance was observed for the most frequent serotypes, mainly serotype 19A. In conclusion, one-quarter of healthy under-five children in Tunisia carried S. pneumoniae in their nasopharynx. A dominance of vaccine serotypes significantly associated with antimicrobial resistance was recorded.

Impact of pneumococcal conjugate vaccination on pneumococcal nasopharyngeal carriage in the Gambia: Population-based cross-sectional surveys

BackgroundThe introduction of pneumococcal conjugate vaccines (PCV) has reduced carriage of vaccine-type (VT) pneumococci in many settings. We determined the impact of The Gambia’s national PCV programme on carriage of VT pneumococci in the population. MethodsSeven-valent PCV (PCV7) was introduced in August 2009 without catch-up and with doses scheduled at 2, 3, 4 months of age; it was replaced by PCV13 in May 2011. We did cross-sectional carriage surveys in 2009, 2015, and 2017 in age-stratified, population-based samples. Nasopharyngeal specimens were collected and processed according to WHO guidelines. We calculated observed and adjusted prevalence ratios (PR) of VT carriage before and after PCV introduction. FindingsWe enrolled 2988, 3162, and 2709 participants in 2009, 2015, and 2017 respectively. The baseline (2009) prevalence of VT pneumococcal carriage among children aged 0–4 years was 42.6 %, which declined to 14.9 % and 17.5 % in 2015 and 2017 respectively (adjPR 0.32 [95 % CI 0.27, 0.38] and 0.38 [0.31, 0.46] respectively). VT prevalence among children aged 5–14 years was 16.6 %, 15.1 %, and 15.8 % in the three surveys (2017 vs 2009, adjPR 0.70 [0.58, 0.83]). VT prevalence among 15–44 year-olds was 6.4 %, 5.7 %, and 7.1 % in the three surveys (2017 vs 2009, adjPR 0.59 [0.46, 0.75]), while in those aged ≥ 45 years it was 4.5 %, 6.5 %, and 4.5 % respectively. Non-VT carriage increased in all age-groups. Prevalent residual serotypes were 34 and 15B (age 0–4 years), 3 and 34 (age 5–14 years), and 3 and 16F (age ≥ 15 years). ConclusionsIntroduction of PCV was associated with reduced VT pneumococcal carriage in young, and older children, although with substantial residual prevalence. Persisting VT, and non-VT, carriage indicate significant, persistent transmission of pneumococci in the population.

Effects of PCV10 and PCV13 on pneumococcal serotype 6C disease, carriage, and antimicrobial resistance

BackgroundThe cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal disease in recent years. A systematic review by the World Health Organization that covered studies through 2016 concluded that available data were insufficient to determine if either PCV10 (which contains serotype 6B but not 6A) or PCV13 (containing serotype 6A and 6B) conferred protection against 6C. MethodsWe performed a systematic review of randomized controlled trials and observational studies published between January 2010 – August 2022 (Medline/Embase), covering the direct, indirect, and overall effect of PCV10 and PCV13 against 6C invasive pneumococcal disease (IPD), non-IPD, nasopharyngeal carriage (NPC), and antimicrobial resistance (AMR). ResultsOf 2548 publications identified, 112 were included. Direct vaccine effectiveness against 6C IPD in children ranged between 70 and 85 % for ≥ 1 dose PCV13 (n = 3 studies), was 94 % in fully PCV13 vaccinated children (n = 2), and −14 % for ≥ 1 dose of PCV10 (n = 1). Compared to PCV7, PCV13 efficacy against 6C NPC in children was 66 % (n = 1). Serotype 6C IPD rates or NPC prevalence declined post-PCV13 in most studies in children (n = 5/6) and almost half of studies in adults (n = 5/11), while it increased post-PCV10 for IPD and non-IPD in all studies (n = 6/6). Changes in AMR prevalence were inconsistent. ConclusionsIn contrast to PCV10, PCV13 vaccination consistently protected against 6C IPD and NPC in children, and provided some level of indirect protection to adults, supporting that serotype 6A but not 6B provides cross-protection to 6C. Vaccine policy makers and regulators should consider the effects of serotype 6A-containing PCVs against serotype 6C disease in their decisions.

Dynamics of Antibiotic Resistance of Streptococcus pneumoniae in France: A Pediatric Prospective Nasopharyngeal Carriage Study from 2001 to 2022

Epidemiological surveillance of nasopharyngeal pneumococcal carriage is important for monitoring serotype distribution and antibiotic resistance, particularly before and after the implementation of pneumococcal conjugate vaccines (PCVs). With a prospective surveillance study in France, we aimed to analyze the dynamics of pneumococcal carriage, antibiotic susceptibility and serotype distribution in children aged 6 to 24 months who had acute otitis media between 2001 and 2022 with a focus on the late PCV13 period from May 2014 to July 2022. Trends were analyzed with segmented linear regression with autoregressive error. For the 17,136 children enrolled, overall pneumococcal carriage was stable during the study. During the late PCV13 period, the five most frequent serotypes were all non-PCV13 serotypes: 15B/C (14.3%), 23B (11.0%), 11A (9.6%), 15A (7.4%) and 35B (6.5%). During the same period, we observed a rebound of penicillin non-susceptibility (+0.15% per month, 95% confidence interval, +0.08 to 0.22, p < 0.001). Five serotypes accounted for 64.4% of the penicillin non-susceptible strains: 11A (17.5%), 35B (14.9%), 15A (13.9%), 15B/C (9.9%) and 19F (8.2%); non-PCV13/PCV15 accounted for <1%, and non-PCV15/PCV20 accounted for 28%. The next generation PCVs, particularly PCV20, may disrupt nasopharyngeal carriage and contribute to decreasing the rate of antibiotic resistance among pneumococci.

Pneumococcal serotypes and antibiotic resistance in healthy carriage children after introduction of PCV13 in Lima, Peru

ObjectiveTo determinate the frequency of Streptococcus pneumoniae nasopharyngeal carriers, serotypes and antimicrobial resistance in healthy children in Lima, Peru, post-PCV13 introduction and to compare the results with a similar study conducted between 2006 and 2008 before PCV7 introduction (pre-PCV7). MethodsA cross-sectional multicenter study was conducted between January 2018 and August 2019 in 1000 healthy children under two years of age. We use standard microbiological methods to determinate S. pneumoniae from nasopharyngeal swab, Kirby Bauer and minimum inhibitory concentration methods to determinate antimicrobial susceptibility and whole genomic sequencing to determinate pneumococcal serotypes. ResultsThe pneumococcal carriage rate was 20.8 % vs. 31.1 % in pre-PCV7 (p < 0.001). The most frequent serotypes were 15C, 19A and 6C (12.4 %, 10.9 % and 10.9 % respectively). The carriage of PCV13 serotypes after PCV13 introduction decreased from 59.1 % (before PCV7 introduction) to 18.7 % (p < 0.001). Penicillin resistance was 75.5 %, TMP/SMX 75.5 % and azithromycin 50.0 %, using disk diffusion. Penicillin resistance rates using MIC breakpoint for meningitis (MIC ≥ 0.12) increased from 60.4 % to 74.5 % (p = 0.001). ConclusionThe introduction of PCV13 in the immunization program in Peru has decreased the pneumococcal nasopharyngeal carriage and the frequency of PCV13 serotypes; however, there has been an increase in non-PCV13 serotypes and antimicrobial resistance.

Update of the consensus document on the aetiology, diagnosis and treatment of acute otitis media and sinusitis

Update of the consensus on acute otitis media (AOM) (2012) and sinusitis (2013) following the introduction of pneumococcal vaccines in the immunization schedule, and related changes, such as epidemiological variation, colonization by of nonvaccine serotypes and emerging antimicrobial resistances. A majority of studies show that the introduction of the pneumococcal 13-valent conjugate vaccine has been followed by a reduction in the nasopharyngeal carriage of pneumococcus, with an increase in the proportion of drug-resistant nonvaccine serotypes. The diagnosis of AOM is still clinical, although more stringent criteria are proposed, which are based on the visualization of abnormalities in the tympanic membrane and the findings of pneumatic otoscopy performed by trained clinicians. The routine diagnosis of sinusitis is also clinical, and the use of imaging is restricted to the assessment of complications. Analgesia with acetaminophen or ibuprofen is the cornerstone of AOM management; watchful waiting or delayed antibiotic prescription may be suitable strategies in select patients. The first-line antibiotic drug in children with AOM and sinusitis and moderate to severe disease is still high-dose amoxicillin, or amoxicillin-clavulanic acid in select cases. Short-course regimens lasting 5–7 days are recommended for patients with uncomplicated disease, no risk factors and a mild presentation. In allergic patients, the selection of the antibiotic agent must be individualized based on severity and whether or not the allergy is IgE-mediated. In recurrent AOM, the choice between watchful waiting, antibiotic prophylaxis or surgery must be individualized based on the clinical characteristics of the patient.

Epidemiology and serotype distribution of Streptococcus pneumoniae carriage among influenza-like illness cases in metropolitan Vientiane, Lao PDR: a community-based cohort study.

Data on the epidemiology of Streptococcus pneumoniae among influenza-like illness (ILI) cases, particularly in low- and middle-income countries are scarce. This study assessed the prevalence, risk factors and serotype distribution of S. pneumoniae carriage among ILI cases in metropolitan Vientiane, Lao People's Democratic Republic. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced among infants in October 2013. Active ILI surveillance was conducted through weekly phone calls in an open community-based cohort study (April 2015-February 2019), involving 5,690 participants from 1,142 randomly selected households. Participants reporting ILI symptoms provided a nasopharyngeal swab and answered a questionnaire. S. pneumoniae and serotype pneumococcal-positive samples were screened by Multiplex PCR assays. Chi-squared tests and generalized linear mixed models were used to test for variables associated with pneumococcal positivity. Among 1,621 ILI episodes, 269 (16.6%) tested positive for nasopharyngeal pneumococcal carriage, with the highest prevalence (55.4%) in children under 5 years. Pneumococcal carriage was significantly associated with concurrent detection of Hemophilus influenzae (adjusted odds ratio [aOR]: 6.93; 95% CI: 2.10-22.9) and exposure to household cigarette smoke (aOR: 1.65; 95% CI: 1.07-2.54). PCV13 serotypes accounted for 37.8% of all pneumococcal isolates. Detection of PCV13 serotypes among ILI cases aged under 5 years declined significantly between 2015/16 and 2018/19. Community-based surveillance of S. pneumoniae among ILI cases complement surveillance at healthcare facilities to provide a more complete picture of pneumococcal carriage. Our findings contribute also to the growing body of evidence on the effects of PCV13 introduction on circulating serotypes and their potential replacement.

Actualización del documento de consenso sobre etiología, diagnóstico y tratamiento de la otitis media aguda y sinusitis

Update of the consensus on acute otitis media (AOM) (2012) and sinusitis (2013) following the introduction of pneumococcal vaccines in the immunization schedule, and related changes, such as epidemiological variation, colonization by of nonvaccine serotypes and emerging antimicrobial resistances. A majority of studies show that the introduction of the pneumococcal 13-valent conjugate vaccine has been followed by a reduction in the nasopharyngeal carriage of pneumococcus, with an increase in the proportion of drug-resistant nonvaccine serotypes. The diagnosis of AOM is still clinical, although more stringent criteria are proposed, which are based on the visualization of abnormalities in the tympanic membrane and the findings of pneumatic otoscopy performed by trained clinicians. The routine diagnosis of sinusitis is also clinical, and the use of imaging is restricted to the assessment of complications. Analgesia with acetaminophen or ibuprofen is the cornerstone of AOM management; watchful waiting or delayed antibiotic prescription may be suitable strategies in select patients. The first-line antibiotic drug in children with AOM and sinusitis and moderate to severe disease is still high-dose amoxicillin, or amoxicillin-clavulanic acid in select cases. Short-course regimens lasting 5–7 days are recommended for patients with uncomplicated disease, no risk factors and a mild presentation. In allergic patients, the selection of the antibiotic agent must be individualized based on severity and whether or not the allergy is IgE-mediated. In recurrent AOM, the choice between watchful waiting, antibiotic prophylaxis or surgery must be individualized based on the clinical characteristics of the patient.

The COVID-19 pandemic as an opportunity for unravelling the causative association between respiratory viruses and pneumococcus-associated disease in young children: a prospective study.

In young children, rates of lower respiratory infections (LRI) and invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of these disease endpoints has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question. This prospective study comprised all children <5 years, living in southern Israel, during 2016 through 2021. The data were previously collected in multiple ongoing prospective surveillance programs and include: hospital visits for community-acquired alveolar pneumonia (CAAP), non-CAAP LRI; nasopharyngeal pneumococcal carriage (<3 years of age); respiratory virus activity; and nationwide, all-ages COVID-19 episodes and IPD in children <5 years. A hierarchical statistical model was developed to estimate the proportion of the different clinical endpoints attributable to each virus from monthly time series data, stratified by age and ethnicity. A separate model was fit for each endpoint, with covariates that included a linear time trend, 12-month harmonic variables to capture unexplained seasonal variations, and the proportion of tests positive for each virus in that month. During 2016 through 2021, 3,204, 26,695, 257, and 619 episodes of CAAP, non-CAAP LRI, pneumococcal bacteremic pneumonia and non-pneumonia IPD, respectively, were reported. Compared to 2016-2019, broad declines in the disease endpoints were observed shortly after the pandemic surge, coincident with a complete disappearance of all PDA-viruses and continued circulation of rhinovirus (RhV) and adenovirus (AdV). From April 2021, off-season and abrupt surges of all disease endpoints occurred, associated with similar dynamics among the PDA-viruses, which re-emerged sequentially. Using our model fit to the entire 2016-2021 period, 82% (95% CI, 75-88%) of CAAP episodes in 2021 were attributable to the common respiratory viruses, as were 22%-31% of the other disease endpoints. Virus-specific contributions to CAAP were: RSV, 49% (95% CI, 43-55%); hMPV, 13% (10-17%); PIV, 11% (7-15%); flu, 7% (1-13%). RhV and AdV did not contribute. RSV was the main contributor in all endpoints, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study. RSV and hMPV play a critical role in the burden of CAAP and pneumococcal disease in children. Interventions targeting these viruses could have a secondary effect on the burden of disease typically attributed to bacteria. There was no funding for this study.

Respiratory Syncytial Virus among Hospitalised Children in an Era of Pneumococcal Vaccination

Background: Acute respiratory tract infection (ARTI) is the leading cause of paediatric hospitalisations in India, especially ≤5 years of age. Aim: The study attempts to investigate RSV disease burden in the under-five and any association between NP carriage and viral ARTI. Methods: This study was conducted from 2019-2020 in Chennai (South India) on hospitalised children with ARTI, between 1 to 60 months of age. Multiplex real-time PCR was employed on nasopharyngeal (NP) samples (n=256) for respiratory pathogens including respiratory syncytial virus (RSV) and Streptococcus pneumoniae (SPN). Results:). Viral and RSV positivity was 81% and 48.6% respectively. Viral co-infections were evidenced in about a quarter of RSV positive children, common being human parechovirus with RSV. Fever, high respiratory rate, severe respiratory distress, cough, difficulty in breathing, chest indrawing and bronchiolitis were significant clinical findings in paediatric viral ARTI. Pneumococcal conjugate vaccine uptake was high (89.4%) in subjects yet 31.87% of vaccinated children had NP pneumococcal carriage. 75% of those with SPN carriage had viral ARTI of which 35.6% were RSV positive. We observed statistically significant association between NP carriage and viral ARTI (p&lt;0.05). Antibiotic usage in suspected RSV versus non-RSV viral ARTI was 68% and 93.8% respectively. Conclusion: Significant RSV disease burden in children &lt; 5 years of age, with ARTI is evidenced with a positive association between SPN carriage and viral acute respiratory tract infections.

Pneumococcal vaccine schedules (PVS) study: a cluster-randomised, non-inferiority trial of an alternative versus standard schedule for pneumococcal conjugate vaccination—statistical analysis plan

RationaleThe effectiveness of universal immunisation with pneumococcal conjugate vaccine (PCV) has been evident in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in several countries. Reducing the cost of PCV programmes may facilitate vaccine introduction in some countries and improve the sustainability of PCV in EPIs in low-income countries when they transition away from subsidised vaccine supply.Methods and designPVS is a real-world field trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. the alternative ‘1+1’ schedule) compared to the standard schedule of three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. the standard ‘3+0’ schedule). Delivery of the interventions began in late 2019 in 68 geographic clusters and will continue for 4 years. The primary endpoint is the prevalence of nasopharyngeal vaccine-type pneumococcal carriage in children aged 2–260 weeks with clinical pneumonia in year 4. Secondary endpoints are the prevalence of vaccine-type pneumococcal carriage among all ages in year 4 and the incidence of radiological pneumonia in children enrolled to receive the interventions. Additional disease and carriage endpoints are included.PurposeThis statistical analysis plan (SAP) describes the cohorts and populations, and follow-up criteria, to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe how analyses will account for the effect of clustering and stratified randomisation. The SAP defines the approach to non-inferiority and other analyses. Defining the SAP early in the trial will avoid bias in analyses that may arise from prior knowledge of trial findings.

Trends in Asymptomatic Nasopharyngeal Streptococcus pneumoniae Carriage with qPCR and Culture Analysis.

We previously reported trends in pneumococcal nasopharyngeal carriage in the post-PCV13 era as detected by conventional culture methods. Our current aim is to assess if there are fundamental differences in the clinical and demographic features of children who have pneumococcal carriage detected by qPCR compared with culture analysis. The CASPER team conducted point-prevalence surveys in 2016 in healthy children in Calgary to determine trends in overall and serotype-specific pneumococcal nasopharyngeal carriage. Being 18 months of age (p = 0.009), having at least one sibling under 2 years of age (p = 0.04), having only sibling(s) over 2 years of age (p = 0.001), and childcare attendance (p = 0.005) were associated with carriage by qPCR methods only. Having only sibling(s) older than 2 years of age was associated with carriage detected by both qPCR and culture methods (p = 0.001). No clinical factors were associated with carriage detected by both qPCR and culture compared to qPCR methods only. Both analyses are suitable methods to detect carriage; however, qPCR analysis is more sensitive and more cost-effective. As there are no fundamental differences in the children that have pneumococcal nasopharyngeal carriage detectable by qPCR methods compared to conventional culture methods, molecular analysis may be a preferable option for future carriage studies.

Nasopharyngeal Carriage of Pneumococcus in Children in England up to 10 Years After 13-Valent Pneumococcal Conjugate Vaccine Introduction: Persistence of Serotypes 3 and 19A and Emergence of 7C.

Monitoring changes in pharyngeal carriage of pneumococcus in children following 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the United Kingdom in 2010 informs understanding of patterns of invasive pneumococcal disease (IPD) incidence. Nasopharyngeal swabs from healthy children vaccinated with PCV13 according to schedule (2, 4, and 12 months) were cultured and serotyped. Results for children aged 13-48 months were compared between 2014-2015 and 2017-2019 and with children aged 6-12 months (2017-2020). Blood was obtained from a subset of children for pneumococcal serotype-specific immunoglobulin G (IgG). Total pneumococcal carriage at 13-48 months was 47.9% (473/988) in 2014-2015 and 51.8% (412/795) in 2017-2019 (P = .10); at age 6-12 months this value was 44.6% (274/615). In 2017-2019, 2.9% (95% confidence interval, 1.8%-4.3%) of children aged 13-48 months carried PCV13 serotypes (mainly 3 [1.5%] and 19A [0.8%]) and >20% carried the additional 20-valent PCV (PCV20) serotypes. Similar proportions of children had IgG ≥0.35 IU/mL for each serotype in 2014-2015 and 2017-2019. Serotype 7C carriage increased significantly (P < .01) between 2014-2015 and 2017-2019. Carriage of PCV20 serotypes 8 and 12F, both major causes of IPD, was rare. Introduction of PCV20, if licensed for children, could significantly change the composition of pneumococcal serotypes carried in the pharynx of UK children. NCT03102840.

Pneumococcal nasopharyngeal carriage in children under 5 years of age at an outpatient healthcare facility in Novi Sad, Serbia during the COVID-19 pandemic

ObjectivesTo assess whether pneumococcal nasopharyngeal carriage among children aged 24–60 months reduced during the coronavirus disease 2019 (COVID-19) pandemic in Novi Sad, Serbia, and to investigate the overall prevalence of carriage, serotype distribution and dominant serotypes 2–3 years after the introduction of pneumococcal conjugate vaccine 10. Design and methodsThis prospective, observational study was conducted in February–March 2020, September–November 2020 and April–June 2021, enabling the comparison of results in the pre-pandemic/early pandemic period with two periods during the COVID-19 pandemic. Pneumococci were identified by standard microbiological methods. Serotype identification was performed using conventional multiplex polymerase chain reaction assays. ResultsAmong 1623 children tested, 515 (31.7%, 95% confidence interval 29.4–34.0%) carried pneumococci. A significant increase in prevalence was found between February–March 2020 and September–November 2020 (P=0.0085), with no difference found between September–November 2020 and April–June 2021 (P=0.0524). Pneumococcal colonization was significantly higher in children who were fully vaccinated and among children who attended day care centres. The dominant serotypes were 15B, 6B, 19F, 11A, 6C, 6A, 3, 23F and 19A, representing 66.4% of all isolates. ConclusionsThis study found that pneumococcal nasopharyngeal carriage in children aged 24–60 months was high before the COVID-19 pandemic, and then increased during the pandemic. This rules out a major role of COVID-19 in the suppression of carriage and, probably, transmission.

Association of Nonpharmaceutical Interventions During the COVID-19 Pandemic With Invasive Pneumococcal Disease, Pneumococcal Carriage, and Respiratory Viral Infections Among Children in France

An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections. To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France. This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France. Implementation of NPIs during the COVID-19 pandemic. The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model. During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, -82% to -43%; P < .001) and was similar for non-13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (-63%; 95% CI, -77% to -48%; P < .001) and low disease potential (-53%; 95% CI, -70% to -35%; P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (-12%; 95% CI, -37% to 12%; P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (-26%; 95% CI, -100% to 52%; P = .50) or low disease potential (-7%; 95% CI, -34% to 20%; P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, -74% to -97%; P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, -55% to -85%; P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, -28% to -78%; P < .001) and 40% (95% CI, -15% to -65%; P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, -7% to 15%; P = .49) of the decrease. In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.

Immunogenicity, otitis media, hearing impairment, and nasopharyngeal carriage 6-months after 13-valent or ten-valent booster pneumococcal conjugate vaccines, stratified by mixed priming schedules: PREVIX_COMBO and PREVIX_BOOST randomised controlled trials

Australian First Nations children are at very high risk of early, recurrent, and persistent bacterial otitis media and respiratory tract infection. With the PREVIX randomised controlled trials, we aimed to evaluate the immunogenicity of novel pneumococcal conjugate vaccine (PCV) schedules. PREVIX_BOOST was a parallel, open-label, outcome-assessor-blinded, randomised controlled trial. Aboriginal children living in remote communities of the Northern Territory of Australia were eligible if they had previously completed the three-arm PREVIX_COMBO randomised controlled trial of the following vaccine schedules: three doses of a 13-valent PCV (PCV13; PPP) or a ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10; SSS) given at 2, 4, and 6 months, or SSS given at 1, 2, and 4 months followed by PCV13 at 6 months (SSSP). At age 12 months, eligible children were randomly assigned by a computer-generated random sequence (1:1, stratified by primary group allocation) to receive either a PCV13 booster or a PHiD-CV10 booster. Analyses used intention-to-treat principles. Co-primary outcomes were immunogenicity against protein D and serotypes 3, 6A, and 19A. Immunogenicity measures were geometric mean concentrations (GMC) and proportion of children with IgG concentrations of 0·35 μg/mL or higher (threshold for invasive pneumococcal disease), and GMCs and proportion of children with antibody levels of 100 EU/mL or higher against protein D. Standardised assessments of otitis media, hearing impairment, nasopharyngeal carriage, and developmental outcomes are reported. These trials are registered with ClinicalTrials.gov (NCT01735084 and NCT01174849). Between April 10, 2013, and Sept 4, 2018, 261 children were randomly allocated to receive a PCV13 booster (n=131) or PHiD-CV10 booster (n=130). Adequate serum samples for pneumococcal serology were obtained from 127 (95%) children in the PCV13 booster group and 126 (97%) in the PHiD-CV10 booster group; for protein D, adequate samples were obtained from 126 (96%) children in the PCV13 booster group and 123 (95%) in the PHiD-CV10 booster group. The proportions of children with IgG concentrations above standard thresholds in PCV13 booster versus PHiD-CV10 booster groups were the following: 71 (56%) of 126 versus 81 (66%) of 123 against protein D (difference 10%, 95% CI -2 to 22), 85 (67%) of 127 versus 59 (47%) of 126 against serotype 3 (-20%, -32 to -8), 119 (94%) of 127 versus 91 (72%) of 126 against serotype 6A (-22%, -31 to -13), and 116 (91%) of 127 versus 108 (86%) of 126 against serotype 19A (-5%, -13 to 3). Infant PCV13 priming mitigated differences between PCV13 and PHiD-CV10 boosters. In both groups, we observed a high prevalence of otitis media (about 90%), hearing impairment (about 75%), nasopharyngeal carriage of pneumococcus (about 66%), and non-typeable H influenzae (about 57%). Of 66 serious adverse events, none were vaccine related. Low antibody concentrations 6 months post-booster might indicate increased risk of pneumococcal infection. The preferred booster was PCV13 if priming did not have PCV13, otherwise either PCV13 or PHiD-CV10 boosters provided similar immunogenicity. Mixed schedules offer flexibility to regional priorities. Non-PCV13 serotypes and non-typeable H influenzae continue to cause substantial disease and disability in Australian First Nation's children. National Health and Medical Research Council (NHMRC).

Factors associated with pneumococcal nasopharyngeal carriage: A systematic review.

Pneumococcal disease is a major contributor to global childhood morbidity and mortality and is more common in low- and middle-income countries (LMICs) than in high-income countries. Pneumococcal carriage is a prerequisite for pneumococcal disease. Pneumococcal conjugate vaccine reduces vaccine-type carriage and disease. However, pneumococcal carriage and disease persist, and it is important to identify other potentially modifiable factors associated with pneumococcal carriage and determine if risk factors differ between low, middle, and high-income countries. This information may help inform pneumococcal disease prevention programs. This systematic literature review describes factors associated with pneumococcal carriage stratified by country income status and summarises pneumococcal carriage rates for included studies. We undertook a systematic search of English-language pneumococcal nasopharyngeal carriage studies up to 30th June 2021. Peer-reviewed studies reporting factors associated with overall pneumococcal nasopharyngeal carriage in healthy, community-based study populations were eligible for inclusion. Two researchers independently reviewed studies to determine eligibility. Results are presented as narrative summaries. This review is registered with PROSPERO, CRD42020186914. Eighty-two studies were included, and 46 (56%) were conducted in LMICs. There was heterogeneity in the factors assessed in each study. Factors positively associated with pneumococcal carriage in all income classification were young age, ethnicity, symptoms of respiratory tract infection, childcare attendance, living with young children, poverty, exposure to smoke, season, and co-colonisation with other pathogens. Breastfeeding and antibiotic use were protective against carriage in all income classifications. Median (interquartile range) pneumococcal carriage rates differed by income classification, ranging from 51% (19.3-70.2%), 38.5% (19.3-51.6%), 31.5% (19.0-51.0%), 28.5% (16.8-35.4%), (P = 0.005) in low-, lower-middle, upper-middle, and high-income classifications, respectively. Our findings suggest that where measured, factors associated with pneumococcal nasopharyngeal carriage are similar across income classifications, despite the highest pneumococcal carriage rates being in low-income classifications. Reducing viral transmission through vaccination and public health interventions to address social determinants of health would play an important role.

Influence of sex, season and environmental air quality on experimental human pneumococcal carriage acquisition: a retrospective cohort analysis.

Streptococcus pneumoniae (pneumococcus) is the most commonly identified bacterial cause of pneumonia and the leading infectious cause of death in children under 5 years of age worldwide. Pneumococcal disease follows a seasonal pattern with increased incidence during winter. Pneumonia burden is also associated with poor air quality. Nasopharyngeal carriage of the bacterium is a pre-requisite of invasive disease.We aimed to determine if susceptibility to nasopharyngeal pneumococcal carriage varied by season and which environmental factors might explain such variation. We also evaluated the influence of sex on susceptibility of carriage. We collated data from five studies in which human volunteers underwent intranasal pneumococcal challenge. Generalised linear mixed-effects models were used to identify factors associated with altered risk of carriage acquisition, specifically climate and air-quality data.During 2011–2017, 374 healthy adults were challenged with type 6B pneumococcus. Odds of carriage were significantly lower in males (OR, 0.61; 95% CI, 0.40–0.92; p=0.02), and higher with cooler temperatures (OR, 0.79; 95% CI, 0.63–0.99; p=0.04). Likelihood of carriage was also associated with lower concentrations of local fine particulate matter concentrations (PM2.5) and increased local rainfall.In contrast to epidemiological series, experimental challenge allowed us to test propensity to acquisition during controlled exposures; immunological explanations for sex and climatic differences should be sought.

Pneumococcal infections and homelessness

SummaryObjectiveTo assess the prevalence of pneumococcal nasopharyngeal carriage, the role of potential risk factors, and the pneumococcal vaccination coverage among sheltered homeless people in Marseille, France.MethodsDuring the winters 2015-2018, we enrolled 571 sheltered homeless males and 54 non-homeless controls. Streptococcus pneumoniae was directly searched from nasal/pharyngeal samples using real-time polymerase chain reaction.ResultsThe homeless people were mostly migrants from African countries, with a mean age of 43 years. Pneumococcal vaccination coverage was low (3.1%). The overall pneumococcal carriage rate was 13.0% and was significantly higher in homeless people (15.3% in 2018) than in controls (3.7%), with p = 0.033. Among homeless people, being aged ≥ 65 years (1.97, 95% CI; 1.01-3.87), living in a specific shelter (OR = 1.80, 95% CI: 1.06-3.05), and having respiratory signs and symptoms at the time of enrolment (OR = 2.55, 95% CI: 1.54-4.21) were independently associated with pneumococcal carriage.ConclusionPneumococcal nasopharyngeal carriage, which is a precursor for pneumococcal disease in at-risk individuals, is frequent among French homeless people. Studies conducted in other countries have also reported outbreaks of pneumococcal infections in homeless people. Pneumococcal vaccination should be systematically considered for sheltered homeless people in France, as is being done in Canada since 2008.